Oxidative stress plays a role in neurodegeneration, regardless of etiology. Physical trauma or secondary effects of insult to the nervous system that result in ischemia can also result in serious damage from oxidative stress. The reduction of oxidative stress is therefore a target for therapeutic interventions for these disorders.
The etiology of Alzheimer's disease is not yet understood. Contributing factors and hallmarks of the disease include an aberrant accumulation of the beta-amyloid fragment (Abeta) of the large transmembrane amyloid precursor protein (APP), abnormal accumulation of calcium within neurons, generation of reactive oxygen species, and abnormal accumulation of phosphorylated forms of the microtubule associated protein, tau. Exposure to Abeta can induce rapid degeneration of cultured neurons. Abeta induces rapid calcium influx, which results in production or reactive oxygen species (ROS), which in turn causes greater accumulation of calcium in the cell. There is also an accumulation of phosphorylated tau. In vitro, phospho-tau is found in paired helical filaments (PHF), structures that persist even after neuronal degeneration and form the “tangles” characteristic of certain neurodegenerative diseases. The physiologic changes caused by Abeta generally result in neuronal death by apoptosis.
Most clinical trials and research related to potential treatments for Alzheimer's disease have examined the efficacy of single compounds, and some treatments have toxic side effects that can limit long-term use. Alzheimer's disease and some other neurodegenerative diseases develop over long periods of time (years). Accordingly, it is desirable that preventative measures and treatments be such that they can be administered over long periods of time without causing significant adverse side effects.